Catalytic activity of the caspase-8–FLIPL complex inhibits RIPK3-dependent necrosis
Open accessAbstract
Caspase-8 has two opposing biological functions--it promotes cell death by triggering the extrinsic pathway of apoptosis, but also has a survival activity, as it is required for embryonic development, T-lymphocyte activation, and resistance to necrosis induced by tumour necrosis factor-α (TNF-α) and related family ligands. Here we show that development of caspase-8-deficient mice is completely rescued by ablation of receptor interacting protein kinase-3 (RIPK3). Adult animals lacking both caspase-8 and RIPK3 display a progressive lymphoaccumulative disease resembling that seen with defects in CD95 or CD95-ligand (also known as FAS and FASLG, respectively), and resist the lethal effects of CD95 ligation in vivo. We have found that caspase-8 prevents RIPK3-dependent necrosis without inducing apoptosis by functioning in a proteolytically active complex with FLICE-like inhibitory protein long (FLIP(L), also known as CFLAR), and this complex is required for the protective function.
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Assembly of necrosome upon TNFR1 stimulation impinges on two conditions: pharmacological or genetic CASP8 inactivation, and RIPK1 deubiquitination-dependent phosphorylation (at least in some settings), which can be favored by SMAC mimetics.
“In addition, the assembly of the necrosome upon TNFR1 stimulation impinges on two conditions: (1) pharmacological or genetic CASP8 inactivation [478, 479], and (2) RIPK1 deubiquitination-dependent phosphorylation (at least in some settings), which can be favored by exogenously provided SMAC mimetics, ensuring the release of RIPK1 from complex I (see above) [334, 335, 480, 481].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [479]
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Two CD95 (APO‐1/Fas) signaling pathways
Scaffidi, C., Fulda, S., Srinivasan, A., Friesen, C., Li, F., Tomaselli, K. J., Debatin, K., Krammer, P. H., & Peter, M. E. (1998) · The EMBO Journal · doi:10.1093/emboj/17.6.1675 · Cited by 3,000 · see citing works
Cho, Y., Challa, S., Moquin, D., Genga, R., Ray, T. D., Guildford, M., & Chan, F. K.-M. (2009) · Cell · doi:10.1016/j.cell.2009.05.037 · Cited by 2,435 · cited 1× · see citing works
“Necrosis induced by TNF in the presence of caspase inhibitors is dependent on the kinase activity of Receptor-Interacting Protein Kinase-1 (RIPK1)4,8 and RIPK39–11, although the mechanisms remain obscure.”
Receptor Interacting Protein Kinase-3 Determines Cellular Necrotic Response to TNF-α
He, S., Wang, L., Miao, L., Wang, T., Du, F., Zhao, L., & Wang, X. (2009) · Cell · doi:10.1016/j.cell.2009.05.021 · Cited by 2,214 · see citing works
Identification of RIP1 kinase as a specific cellular target of necrostatins
Degterev, A., Hitomi, J., Germscheid, M., Ch'en, I. L., Korkina, O., Teng, X., Abbott, D., Cuny, G. D., Yuan, C., Wagner, G., et al. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.83 · Cited by 2,059 · cited 1× · see citing works
“Necrosis induced by TNF in the presence of caspase inhibitors is dependent on the kinase activity of Receptor-Interacting Protein Kinase-1 (RIPK1)4,8 and RIPK39–11, although the mechanisms remain obscure.”
Holler, N., Zaru, R., Micheau, O., Thome, M., Attinger, A., Valitutti, S., Bodmer, J.-L., Schneider, P., Seed, B., & Tschopp, J. (2000) · Nature Immunology · doi:10.1038/82732 · Cited by 1,932 · cited 12× · see citing works
“Cleaved caspase-8 was observed in whole lysates from these cells upon FLIP knockdown and TNF treatment, indicating that active caspase-8 was present in these cells, but was unable to prevent formation of the RIPK1-RIPK3 complex in the absence of FLIP (fig.”
InfluentialRIP3, an Energy Metabolism Regulator That Switches TNF-Induced Cell Death from Apoptosis to Necrosis
Zhang, D.-W., Shao, J., Lin, J., Zhang, N., Lu, B.-J., Lin, S.-C., Dong, M.-Q., & Han, J. (2009) · Science · doi:10.1126/science.1172308 · Cited by 1,931 · see citing works
Lethal effect of the anti-Fas antibody in mice
Ogasawara, J., Watanabe-Fukunaga, R., Adachi, M., Matsuzawa, A., Kasugai, T., Kitamura, Y., Itoh, N., Suda, T., & Nagata, S. (1993) · Nature · doi:10.1038/364806a0 · Cited by 1,881 · see citing works
Varfolomeev, E., Schuchmann, M., Luria, V., Chiannilkulchai, N., Beckmann, J., Mett, I., Rebrikov, D., Brodianski, V. M., Kemper, O., Kollet, O., et al. (1998) · Immunity · doi:10.1016/s1074-7613(00)80609-3 · Cited by 1,332 · see citing works
Vercammen, D., Beyaert, R., Denecker, G., Goossens, V., Loo, G., Declercq, W., Grooten, J., Fiers, W., & Vandenabeele, P. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.187.9.1477 · Cited by 925 · see citing works
FADD: Essential for Embryo Development and Signaling from Some, But Not All, Inducers of Apoptosis
Yeh, W., de la Pompa, J. L., McCurrach, M. E., Shu, H., Elia, A., Shahinian, A., Ng, M. S. W., Wakeham, A. C., Khoo, W., Mitchell, K., et al. (1998) · Science · doi:10.1126/science.279.5358.1954 · Cited by 886 · see citing works
NF-κB Signals Induce the Expression of c-FLIP
Micheau, O., Lens, S. M. A., Gaide, O., Alevizopoulos, K., & Tschopp, J. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.16.5299-5305.2001 · Cited by 809 · see citing works
Death receptor signal transducers: nodes of coordination in immune signaling networks
Wilson, N., Dixit, V., & Ashkenazi, A. (2009) · Nature Immunology · doi:10.1038/ni.1714 · Cited by 569 · see citing works
c‐FLIPL is a dual function regulator for caspase‐8 activation and CD95‐mediated apoptosis
Chang, D. W.-W., Xing, Z., Pan, Y., Algeciras‐Schimnich, A., Barnhart, B. C., Yaish‐Ohad, S., Peter, M. E., & Yang, X. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf356 · Cited by 560 · see citing works
Virus Inhibition of RIP3-Dependent Necrosis
Upton, J. W., Kaiser, W. J., & Mocarski, E. S. (2010) · Cell Host & Microbe · doi:10.1016/j.chom.2010.03.006 · Cited by 559 · see citing works
Newton, K., Sun, X., & Dixit, V. M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.4.1464-1469.2004 · Cited by 544 · see citing works
Target Protease Specificity of the Viral Serpin CrmA
Zhou, Q., Snipas, S. J., Orth, K., Muzio, M., Dixit, V. M., & Salvesen, G. S. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.12.7797 · Cited by 520 · see citing works
Self-citationEssential role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity.Preprint
Salmena, L., Lemmers, B., Hakem, A., Matysiak-Zablocki, E., Murakami, K., Au, P. Y. B., Berry, D., Tamblyn, L., Shehabeldin, A., Migon, E., et al. (2003) · Genes & Development · doi:10.1101/gad.1063703 · Cited by 517 · see citing works
Self-citationYeh, W.-C., Itie, A., Elia, A. J., Ng, M., Shu, H.-B., Wakeham, A., Mirtsos, C., Suzuki, N., Bonnard, M., Goeddel, D. V., et al. (2000) · Immunity · doi:10.1016/s1074-7613(00)80214-9 · Cited by 515 · see citing works
Requirement for Caspase-8 in NF-κB Activation by Antigen Receptor
Su, H. C., Bidère, N., Zheng, L., Cubre, A., Sakai, K., Dale, J. K., Salmena, L., Hakem, R., Straus, S. E., & Lenardo, M. J. (2005) · Science · doi:10.1126/science.1104765 · Cited by 427 · see citing works
Self-citationThe multifaceted role of Fas signaling in immune cell homeostasis and autoimmunity
Siegel, R. M., Chan, F. K.-M., Chun, H. J., & Lenardo, M. J. (2000) · Nature Immunology · doi:10.1038/82712 · Cited by 423 · see citing works
Cellular IAPs inhibit a cryptic CD95-induced cell death by limiting RIP1 kinase recruitment
Geserick, P., Hupe, M., Moulin, M., Wong, W., Feoktistova, M., Kellert, B., Gollnick, H., Silke, J., & Leverkus, M. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200904158 · Cited by 258 · see citing works
Activation of caspases-8 and -10 by FLIPL
Boatright, K. M., Cristina, D. E. I. S., Denault, J., Sutherlin, D. P., & Salvesen, G. S. (2004) · Biochemical Journal · doi:10.1042/bj20040809 · Cited by 242 · cited 1× · see citing works
“Biochemical and structural studies have indicated that FLIP can heterodimerize with caspase-8 in kosmotropic salt, and that this complex may be able to impart catalytic activity on caspase-8 in the absence of interdomain cleavage18,19.”
Self-citationGranzyme B Is Inhibited by the Cowpox Virus Serpin Cytokine Response Modifier A
Quan, L. T., Caputo, A., Bleackley, R. C., Pickup, D. J., & Salvesen, G. S. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.18.10377 · Cited by 234 · see citing works
Self-citationPop, C., Oberst, A., Drąg, M., van Raam, B. J., Riedl, S. J., Green, D. R., & Salvesen, G. S. (2011) · Biochemical Journal · doi:10.1042/bj20101738 · Cited by 225 · cited 1× · see citing works
“In cell-free systems, caspase-8-FLIP heterodimers display less proteolytic activity than caspase-8 homodimers on apoptotic substrates such as Bid and caspase-317,30, while maintaining a low but perceptible ability to cleave RIPK130.”
Self-citationOberst, A., Pop, C., Tremblay, A. G., Blais, V., Denault, J.-B., Salvesen, G. S., & Green, D. R. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.095083 · Cited by 214 · cited 1× · see citing works
“S3a)16, hetero-dimerization of this non-cleavable caspase-8 with FRB-FLIP was enzymatically active (Fig.”
Self-citationHughes, M. A., Harper, N. W., Butterworth, M., Cain, K., Cohen, G. M., & MacFarlane, M. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.06.012 · Cited by 185 · cited 3× · see citing works
“Apoptosis mediated by caspase-8 depends on cleavage of the caspase16,17, while inhibition of RIPK3-mediated cell death does not.”
Smith, K. G. C., Strasser, A., & Vaux, D. L. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00901.x · Cited by 169 · see citing works
Antigen-mediated T cell expansion regulated by parallel pathways of death
Ch’en, I. L., Beisner, D. R., Degterev, A., Lynch, C., Yuan, J., Hoffmann, A., & Hedrick, S. Μ. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808043105 · Cited by 141 · see citing works
Role of Proteolysis in Caspase-8 Activation and Stabilization
Pop, C., Fitzgerald, P., Green, D. R., & Salvesen, G. S. (2007) · Biochemistry · doi:10.1021/bi602623b · Cited by 139 · cited 1× · see citing works
“In contrast, apoptosis induced by caspase-8 depends on such cleavage, which stabilizes the homo-dimer15–17,23.”
Self-citationKang, T., Oh, G., Scandella, E., Bolinger, B., Ludewig, B., Kovalenko, A., & Wallach, D. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.4.2522 · Cited by 138 · see citing works
Caspase-8 Is Involved in Neovascularization-Promoting Progenitor Cell Functions
Scharner, D., Rössig, L., Carmona, G., Chavakis, E., Urbich, C., Fischer, A., Kang, T., Wallach, D., Chiang, Y. J., Lissanu, Y., et al. (2009) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.108.182006 · Cited by 24 · see citing works
Activation of Procaspases by FK506 Binding Protein-Mediated Oligomerization
Chang, D. W.-W., & Yang, X. (2003) · Science s STKE · doi:10.1126/stke.2003.167.pl1 · Cited by 13 · see citing works
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Research works printed but not linked: 2
- [32]Geserick P Cellular IAPs inhibit a cryptic CD95-induced cell death by limiting RIP1 kinase recruitment J Cell Biol 2009 187 1037 1054 20038679 PMC2806279
- [34]Oberst A Inducible dimerization and inducible cleavage reveal a requirement for both processes in caspase-8 activation J Biol Chem 285 16632 16642 20308068 PMC2878047
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Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680 · see citing works
Self-citationMixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of RIP3 Kinase
Sun, L., Wang, H., Wang, Z., He, S., Chen, S., Liao, D., Wang, L., Yan, J., Liu, W., Lei, X., et al. (2012) · Cell · doi:10.1016/j.cell.2011.11.031 · Cited by 2,698 · see citing works
“This indicates that the cardiac, vascular, and hematopoietic defects that occur during the development of caspase-8 knockout mice are caused by RIP3-mediated necrosis, unleashed by disrupting caspase-8 expression (Kaiser et al., 2011; Oberst et al., 2011).”
Caspase Functions in Cell Death and DiseasePreprint
McIlwain, D. R., Berger, T., & Mak, T. W. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008656 · Cited by 2,607 · see citing works
“Recently, three reports provided evidence that some of the defects associated with loss of caspase-8, and result in embryonic death, are not owing to impaired apoptosis but rather to defective suppression of receptor-interacting serinethreonine kinase 3 (RIPK3) -dependent necrosis (Kaiser et al. 2011; Oberst et al. 20…”
BackgroundNecroptosis and its role in inflammation
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Necroptosis, pyroptosis and apoptosis: an intricate game of cell death
Bertheloot, D., Latz, E., & Franklin, B. S. (2021) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-00630-3 · Cited by 2,198 · see citing works
Antioxidants Maintain Cellular Redox Homeostasis by Elimination of Reactive Oxygen Species
He, L., He, T., Farrar, S., Ji, L., Liu, T., & Ma, X. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000485089 · Cited by 2,142 · see citing works
Glutaminolysis and transferrin regulate ferroptosis
Gao, M., Monian, P., Quadri, N., Ramasamy, R., & Jiang, X. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.06.011 · Cited by 2,069 · see citing works
“However, RIP3 gene deletion did not prevent serum-induced cell death in MEFs, although it completely blocked TNFα-induced necrosis as predicted (Figure 1F, G and Figure S1C).”
BackgroundInfluentialKarki, R., Sharma, B. R., Tuladhar, S., Williams, E. P., Zalduondo, L., Samir, P., Zheng, M., Sundaram, B., Banoth, B., Malireddi, R. K. S., et al. (2021) · Cell · doi:10.1016/j.cell.2020.11.025 · Cited by 1,734 · see citing works
Regulated necrosis: the expanding network of non-apoptotic cell death pathways
Berghe, T. V., Linkermann, A., Jouan-Lanhouet, S., Walczak, H., & Vandenabeele, P. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3737 · Cited by 1,735 · see citing works
Necroptosis: The Release of Damage-Associated Molecular Patterns and Its Physiological Relevance
Kaczmarek, A., Vandenabeele, P., & Krysko, D. V. (2013) · Immunity · doi:10.1016/j.immuni.2013.02.003 · Cited by 1,411 · see citing works
Plasma membrane translocation of trimerized MLKL protein is required for TNF-induced necroptosis
Cai, Z., Jitkaew, S., Zhao, J., Chiang, H.-C., Choksi, S., Liu, J., Ward, Y., Wu, L.-G., & Liu, Z.-G. (2014) · Nature Cell Biology · doi:10.1038/ncb2883 · Cited by 1,322 · see citing works
Li, J., McQuade, T., Siemer, A. B., Napetschnig, J., Moriwaki, K., Hsiao, Y.-S., Damko, E., Moquin, D., Walz, T., McDermott, A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.06.019 · Cited by 1,222 · see citing works
“…critical for preventing extensive necrosis during embryonic development in order to ensure proper clonal expansion of lymphocytes and to prevent extensive necrosis and inflammation in skin and intestinal epithelium (Kaiser et al., 2011; Oberst et al., 2011; Welz et al., 2011; Zhang et al., 2011).”
Synchronized renal tubular cell death involves ferroptosis
Linkermann, A., Skouta, R., Himmerkus, N., Mulay, S. R., Dewitz, C., De Zen, F., Prokai, A., Zuchtriegel, G., Krombach, F., Welz, P.-S., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1415518111 · Cited by 1,126 · see citing works
“We applied active (16-86) and inactive (16-79) compounds to a model of severe ischemia–reperfusion injury (IRI), which we described before (4).”
MethodSelf-citationMonocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span
Misharin, A. V., Morales-Nebreda, L., Reyfman, P. A., Cuda, C. M., Walter, J. M., McQuattie-Pimentel, A. C., Chen, C.-I., Anekalla, K. R., Joshi, N., Williams, K. J. N., et al. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20162152 · Cited by 1,133 · see citing works
“Caspase-8 initiates apoptosis through caspase-3/7 activation and blocks necroptosis via suppression of RIPK1–RIPK3 signaling (Hutcheson and Perlman, 2008; Oberst et al., 2011).”
BackgroundFricker, M., Tolkovsky, A. M., Borutaitė, V., Coleman, M. P., & Brown, G. C. (2018) · Physiological Reviews · doi:10.1152/physrev.00011.2017 · Cited by 1,122 · see citing works
Cell Death SignalingPreprint
Green, D. R., & Llambi, F. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a006080 · Cited by 1,117 · see citing works
“However, in the absence of FLIP, activation of caspase-8 is not sufficient to prevent RIPK-dependent necrosis, even if apoptosis downstream from caspase-8 activation is blocked (Oberst et al. 2011).”
BackgroundSelf-citationCaspase-8 is the molecular switch for apoptosis, necroptosis and pyroptosis
Fritsch, M., Günther, S. D., Schwarzer, R., Albert, M., Schorn, F., Werthenbach, J. P., Schiffmann, L. M., Stair, N., Stocks, H., Seeger, J. M., et al. (2019) · Nature · doi:10.1038/s41586-019-1770-6 · Cited by 1,122 · see citing works
Linkermann, A., & Green, D. R. (2014) · New England Journal of Medicine · doi:10.1056/nejmra1310050 · Cited by 1,103 · see citing works
Self-citationPyroptosis versus necroptosis: similarities, differences, and crosstalk
Frank, D., & Vince, J. E. (2019) · Cell Death & Differentiation · doi:10.1038/s41418-018-0212-6 · Cited by 1,062 · see citing works
Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy
Gao, W., Wang, Y., Zhou, Y., Wang, X., & Yu, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01046-3 · Cited by 1,069 · see citing works
Necroptosis in development, inflammation and disease
Weinlich, R., Oberst, A., Beere, H. M., & Green, D. R. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.149 · Cited by 1,016 · see citing works
Self-citationProgrammed cell death as a defence against infection
Jørgensen, I., Rayamajhi, M., & Miao, E. A. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2016.147 · Cited by 1,014 · see citing works
Essential versus accessory aspects of cell death: recommendations of the NCCD 2015
Galluzzi, L., Bravo-San Pedro, J. M., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Alnemri, E. S., Altucci, L., Andrews, D., Annicchiarico-Petruzzelli, M., et al. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2014.137 · Cited by 1,002 · see citing works
Self-citationNewton, K., Strasser, A., Kayagaki, N., & Dixit, V. M. (2024) · Cell · doi:10.1016/j.cell.2023.11.044 · Cited by 1,029 · see citing works
Regulation of tumour necrosis factor signalling: live or let die
Brenner, D., Blaser, H., & Mak, T. W. (2015) · Nature Reviews Immunology · doi:10.1038/nri3834 · Cited by 998 · see citing works
“This crucial interplay between the inhibition of caspase activity and RIPK1-and RIPK3-mediated necrotic cell death has been clearly demonstrated by the finding that genetic deletion of RIPK1 and/or RIPK3 rescues the lethality observed in caspase 8-deficient or FADD-deficient mice 86,87,106–108 .”
BackgroundEmerging connectivity of programmed cell death pathways and its physiological implications
Bedoui, S., Herold, M. J., & Strasser, A. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0270-8 · Cited by 986 · see citing works
Fundamental Mechanisms of Regulated Cell Death and Implications for Heart Disease
Re, D. P. D., Amgalan, D., Linkermann, A., Liu, Q., & Kitsis, R. N. (2019) · Physiological Reviews · doi:10.1152/physrev.00022.2018 · Cited by 979 · see citing works
Toll-like Receptor 3-mediated Necrosis via TRIF, RIP3, and MLKL
Kaiser, W. J., Sridharan, H., Huang, C., Mandal, P., Upton, J. W., Gough, P. J., Sehon, C. A., Marquis, R. W., Bertin, J., & Mocarski, E. S. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.462341 · Cited by 959 · see citing works
“This situation is reminiscent of work from Meylan et al. (29), where RIP1 and RIP3 were shown to differentially compete for RHIM-depen-dent binding with TRIF.”
BackgroundResultInfluentialA guide to cell death pathways
Yuan, J., & Ofengeim, D. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00689-6 · Cited by 972 · see citing works
“Furthermore, blocking RIPK1 kinase and necroptosis can suppress early embryonic lethality of Casp8 -null mice, Fadd -null mice, Abin1 -null mice and Tbk1 - null mice, suggesting that necroptosis may be involved in the removal of defective developing embryos 52,67,139,140 .”
Death by TNF: a road to inflammation
Loo, G., & Bertrand, M. J. M. (2022) · Nature reviews. Immunology · doi:10.1038/s41577-022-00792-3 · Cited by 977 · see citing works
Caspases in Cell Death, Inflammation, and Pyroptosis
Kesavardhana, S., Malireddi, R. K. S., & Kanneganti, T. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-073119-095439 · Cited by 927 · see citing works
“However, recruitment of cFLIP to the ripoptosome complex diverts the apoptotic activity of caspase-8 to prosurvival inflammatory signaling (1, 21, 25, 56, 57).”
BackgroundWang, Z., Jiang, H., Chen, S., Du, F., & Wang, X. (2012) · Cell · doi:10.1016/j.cell.2011.11.030 · Cited by 949 · see citing works
“…of necrotic cell death (also known as necroptosis) has been implicated in development , tissue damage during acute pancreatitis, retinal detachment , and antiviral immunity (Cho et al., 2009b; He et al., 2009; Kaiser et al., 2011; Oberst et al., 2011; Trichonas et al., 2010; Upton et al., 2010).”
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Günther, C., Martini, E., Wittkopf, N., Amann, K., Weigmann, B., Neumann, H., Waldner, M. J., Hedrick, S. Μ., Tenzer, S., Neurath, M. F., et al. (2011) · Nature · doi:10.1038/nature10400 · Cited by 882 · see citing works
“This has been highlighted by genetic studies demonstrating that deletion of RIP3 can rescue the embryonic lethality observed in mice with a general deletion of caspase-8 19,20 .”
Feoktistova, M., Geserick, P., Kellert, B., Panayotova‐Dimitrova, D., Langlais, C., Hupe, M., Cain, K., MacFarlane, M., Häcker, G. A., & Leverkus, M. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.06.011 · Cited by 855 · see citing works
Kuriakose, T., Man, S. M., Subbarao Malireddi, R. K., Karki, R., Kesavardhana, S., Place, D. E., Neale, G., Vogel, P., & Kanneganti, T.-D. (2016) · Science Immunology · doi:10.1126/sciimmunol.aag2045 · Cited by 818 · see citing works
Tenev, T., Bianchi, K., Darding, M., Broemer, M., Langlais, C., Wållberg, F., Zachariou, A., Lopez, J. S., MacFarlane, M., Cain, K., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.06.006 · Cited by 818 · see citing works
“…that FADD, caspase-8, and FLIP, which resembles caspase-8 but lacks a catalytically active residue (Wilson et al., 2009), are required for embryonic development and T-lymphocyte activation by inhibiting RIP-dependent necrosis (Gentle et al., 2011; Kaiser et al., 2011; Oberst et al., 2011).”
BackgroundJulien, O., & Wells, J. A. (2017) · Cell Death & Differentiation · doi:10.1038/cdd.2017.44 · Cited by 816 · see citing works
“caspase-8 can suppress necroptosis is not fully understood, but it appears that its catalytic activity is necessary.(81)”
BackgroundCaMKII is a RIP3 substrate mediating ischemia- and oxidative stress–induced myocardial necroptosis
Zhang, T., Zhang, Y., Cui, M., Jin, L., Wang, Y., Lv, F., Liu, Y., Zheng, W., Shang, H., Zhang, J., et al. (2016) · Nature Medicine · doi:10.1038/nm.4017 · Cited by 790 · see citing works
AIM2 forms a complex with pyrin and ZBP1 to drive PANoptosis and host defence
Lee, S., Karki, R., Wang, Y., Nguyen, L. N., Kalathur, R., & Kanneganti, T. (2021) · Nature · doi:10.1038/s41586-021-03875-8 · Cited by 802 · see citing works
Human Monocytes Engage an Alternative Inflammasome Pathway
Gaidt, M. M., Ebert, T. S., Chauhan, D., Schmidt, T., Schmid-Burgk, J. L., Rapino, F. A., Robertson, A. A. B., Cooper, M. A., Graf, T., & Hornung, V. (2016) · Immunity · doi:10.1016/j.immuni.2016.01.012 · Cited by 780 · see citing works
“…FasR requires both catalytic caspase activity and auto-proteolysis, caspase-8-mediated inhibition of TNF-mediated necroptosis was shown to require catalytic caspase activity only, with a heterodimer of caspase-8:cFLIP being operational in this setting (Oberst and Green, 2011; Oberst et al., 2011).”
Upton, J. W., Kaiser, W. J., & Mocarski, E. S. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.01.016 · Cited by 758 · see citing works
“Likewise, the RIP3-dependent necroptosis resulting in lethality of Casp8−/− mice (Kaiser et al., 2011; Oberst et al., 2011) was not rescued loss of DAI (Figure S3D), and Casp8−/−DAI−/− embryos were phenotypically indistinguishable from Casp8−/− littermate embryos (data not shown).”
InfluentialCaspase‐8: regulating life and death
Tummers, B., & Green, D. R. (2017) · Immunological Reviews · doi:10.1111/imr.12541 · Cited by 754 · see citing works
Self-citationMalireddi, R. K. S., Kesavardhana, S., & Kanneganti, T. (2019) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2019.00406 · Cited by 750 · see citing works
“Studies focused on the RHIM domain-containing proteins (RIPK1 and RIPK3) and their crosstalk with FADD–caspase-8–mediated pathways improved our understanding of the apoptotic and necroptotic pathways and their intricate regulatory mechanisms (Holler et al., 2000; He et al., 2009; Zhang et al., 2009; Gunther et al., 20…”
BackgroundHe, S., Liang, Y., Shao, F., & Wang, X. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1116302108 · Cited by 725 · see citing works
“One possible explanation for this apparent paradox is that the RIP1-mediated signal, and possibly the induction of cFLIP [cellular FLICE (FADD-like IL-1β–converting enzyme)inhibitory protein], is particularly important for macrophage survival (25).”
BackgroundNecroptosis: a regulated inflammatory mode of cell death
Dhuriya, Y. K., & Sharma, D. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1235-0 · Cited by 725 · see citing works
“Hence, complex I is a crucial checkpoint for cell survival and necroptosis [31].”
BackgroundNecroptosis: Mechanisms and Relevance to Disease
Galluzzi, L., Kepp, O., Chan, F. K.-M., & Kroemer, G. (2016) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-052016-100247 · Cited by 721 · see citing works
“5 (60), such an embryonic lethal phenotype is rescued by the concomitant absence of Ripk3 (56, 61).”
ESCRT-III Acts Downstream of MLKL to Regulate Necroptotic Cell Death and Its Consequences
Gong, Y.-N., Guy, C., Olauson, H., Becker, J. U., Yang, M., Fitzgerald, P., Linkermann, A., & Green, D. R. (2017) · Cell · doi:10.1016/j.cell.2017.03.020 · Cited by 689 · see citing works
“As a consequence, necroptosis is induced by a number of conditions, including TLR and TNFR ligation, provided FADD-caspase-8-FLIP activity is inhibited or disrupted (Vanden Berghe et al., 2016).”
Self-citationActivity of Protein Kinase RIPK3 Determines Whether Cells Die by Necroptosis or Apoptosis
Newton, K., Dugger, D. L., Wickliffe, K. E., Kapoor, N., de Almagro, M. C., Vucic, D., Komuves, L., Ferrando, R. E., French, D. M., Webster, J., et al. (2014) · Science · doi:10.1126/science.1249361 · Cited by 687 · see citing works
Converging roles of caspases in inflammasome activation, cell death and innate immunity
Man, S. M., & Kanneganti, T. (2015) · Nature reviews. Immunology · doi:10.1038/nri.2015.7 · Cited by 701 · see citing works
Martinez, J., Almendinger, J., Oberst, A., Ness, R., Dillon, C. P., Fitzgerald, P., Hengartner, M. O., & Green, D. R. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1113421108 · Cited by 655 · see citing works
“The PtdSer receptor TIM4 has been demonstrated to play a critical role in the recognition and clearance of apoptotic cells in vivo (6).”
BackgroundMethodInfluentialSelf-citationRetractedMetabolic control of cell death
Green, D. R., Galluzzi, L., & Kroemer, G. (2014) · Science · doi:10.1126/science.1250256 · Cited by 661 · see citing works
Self-citationRegulated necrosis: disease relevance and therapeutic opportunities
Conrad, M., Angeli, J. P. F., Vandenabeele, P., & Stockwell, B. R. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2015.6 · Cited by 630 · see citing works
Live to die another way: modes of programmed cell death and the signals emanating from dying cells
Fuchs, Y., & Steller, H. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3999 · Cited by 632 · see citing works
Cellular Mechanisms Controlling Caspase Activation and FunctionPreprint
Parrish, A. B., Freel, C. D., & Kornbluth, S. A. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008672 · Cited by 627 · see citing works
“Interestingly, in contrast to the proapoptotic caspase-8 homodimer, these heterodimers of caspase-8 and FLIPL have been shown to promote cell survival (Oberst et al. 2011; van Raam and Salvesen 2012).”
BackgroundRegulation of RIP1 kinase signalling at the crossroads of inflammation and cell death
Ofengeim, D., & Yuan, J. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3683 · Cited by 615 · see citing works
RIP3 Induces Apoptosis Independent of Pronecrotic Kinase Activity
Mandal, P., Berger, S. B., Pillay, S., Moriwaki, K., Huang, C., Guo, H., Lich, J. D., Finger, J. N., Kasparcova, V., Votta, B. J., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.10.021 · Cited by 619 · see citing works
“We thank Tak Mak (University of Toronto) for cFLIP / MEF and Fadd / MEF, Astar Winoto (University of California Berkeley) for FADD antibody, Domagoj Vucic (Genentech) for BV6, and Andrew Oberst (University ofWashington) for cFLIP expression plasmids.”
BackgroundInfluentialFADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation
Welz, P.-S., Wullaert, A., Vlantis, K., Kondylis, V., Fernández-Majada, V., Ermolaeva, M., Kirsch, P., Sterner-Kock, A., van Loo, G., & Pasparakis, M. (2011) · Nature · doi:10.1038/nature10273 · Cited by 594 · see citing works
RIPK1 Regulates RIPK3-MLKL-Driven Systemic Inflammation and Emergency Hematopoiesis
Rickard, J. A., O’Donnell, J. A., Evans, J. M., Lalaoui, N., Poh, A. R., Rogers, T., Vince, J. E., Lawlor, K. E., Ninnis, R. L., Anderton, H., et al. (2014) · Cell · doi:10.1016/j.cell.2014.04.019 · Cited by 589 · see citing works
RIP Kinase-Dependent Necrosis Drives Lethal Systemic Inflammatory Response Syndrome
Duprez, L., Takahashi, N., Hauwermeiren, F. V., Vandendriessche, B., Goossens, V., Berghe, T. V., Declercq, W., Libert, C., Cauwels, A., & Vandenabeele, P. (2011) · Immunity · doi:10.1016/j.immuni.2011.09.020 · Cited by 591 · see citing works
“These in vitro results are in line with the recent reports on the in vivo role of caspase-8 as a physiological inhibitor of RIPK3-mediated necroptosis (Kaiser et al., 2011; Oberst et al., 2011).”
BackgroundResultChristgen, S., Zheng, M., Kesavardhana, S., Karki, R., Malireddi, R. K. S., Banoth, B., Place, D. E., Briard, B., Sharma, B. R., Tuladhar, S., et al. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.00237 · Cited by 588 · see citing works
“, 2004), Ripk3Casp8 (Oberst et al., 2011), and Casp1/11Ripk3Casp8 (Gurung et al.”
Exploring the TRAILs less travelled: TRAIL in cancer biology and therapy
von Karstedt, S., Montinaro, A., & Walczak, H. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.28 · Cited by 556 · see citing works
RIPK1 Blocks Early Postnatal Lethality Mediated by Caspase-8 and RIPK3
Dillon, C. P., Weinlich, R., Rodriguez, D. A., Cripps, J. G., Quarato, G., Gurung, P., Verbist, K. C., Brewer, T. L., Llambi, F., Gong, Y.-N., et al. (2014) · Cell · doi:10.1016/j.cell.2014.04.018 · Cited by 562 · see citing works
Self-citationLinkermann, A., Chen, G., Dong, G., Kunzendorf, U., Krautwald, S., & Dong, Z. (2014) · Journal of the American Society of Nephrology · doi:10.1681/asn.2014030262 · Cited by 564 · see citing works
Gurung, P., Anand, P., Malireddi, R. K. S., Walle, L. V., Opdenbosch, N. V., Dillon, C. P., Weinlich, R., Green, D. R., Lamkanfi, M., & Kanneganti, T. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1302839 · Cited by 558 · see citing works
“To this end, we differentiated BMDMs from caspase-8–deficient mice in a RIP3-deficient background (14), as well as from animals with a conditionally targeted deletion of caspase-8 in myeloid progenitors cells (Casp8) (33).”
Self-citationRIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis
Dannappel, M., Vlantis, K., Kumari, S., Polykratis, A., Kim, C., Wachsmuth, L., Eftychi, C., Lin, J., Corona, T., Hermance, N., et al. (2014) · Nature · doi:10.1038/nature13608 · Cited by 534 · see citing works
Two independent pathways of regulated necrosis mediate ischemia–reperfusion injury
Linkermann, A., Bräsen, J. H., Darding, M., Jin, M. K., Sanz, A. B., Heller, J.-O., Zen, F. D., Weinlich, R., Ortíz, A., Walczak, H., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1305538110 · Cited by 568 · see citing works
“The relevance of necroptosis has been clearly demonstrated by the reversal of the lethal phenotype of caspase-8–deficient mice on a RIPK3-knockout (ko) background (16, 17).”
BackgroundSelf-citationFrom big data analysis to personalized medicine for all: challenges and opportunities
Alyass, A., Turcotte, M., & Meyre, D. (2015) · BMC Medical Genomics · doi:10.1186/s12920-015-0108-y · Cited by 557 · see citing works
“…has opposing biological functions as it promotes cell death by triggering the extrinsic pathway of apoptosis, while having beneficial effects on cell survival through embryonic development, T-lymphocyte activation, and resistance to necrosis induced by tumor necrosis factor-α (TNF-α ) [68].”
BackgroundProgrammed necrosis in inflammation: Toward identification of the effector molecules
Wallach, D., Kang, T., Dillon, C. P., & Green, D. R. (2016) · Science · doi:10.1126/science.aaf2154 · Cited by 547 · see citing works
“Strong negative regulation of the initiation of signaling for necroptosis is mediated by caspase-8 together with a caspase-like molecule, c-FLIPL (16, 27, 28), and by the ubiquitin ligases cIAP1 and cIAP2 (29).”
BackgroundSelf-citationCleavage of RIPK1 by caspase-8 is crucial for limiting apoptosis and necroptosis
Newton, K., Wickliffe, K. E., Dugger, D. L., Maltzman, A., Roose‐Girma, M., Dohse, M., Kömüves, L. G., Webster, J. D., & Dixit, V. M. (2019) · Nature · doi:10.1038/s41586-019-1548-x · Cited by 547 · see citing works
Wang, Y., & Kanneganti, T.-D. (2021) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2021.07.038 · Cited by 545 · see citing works
“Embryonic lethality of Casp8 (cid:1) / (cid:1) mice can be rescued by loss of necroptotic pathway effectors Ripk3 or Mlkl , suggesting a predominant role of apoptotic CASP8 in preventing necroptosis during development; indeed, both RIPK1 and RIPK3 are substrates for CASP8 [104– 107].”
BackgroundDeciphering the rules of programmed cell death to improve therapy of cancer and other diseases
Strasser, A., Cory, S., & Adams, J. M. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.307 · Cited by 530 · see citing works
Tumour-cell-induced endothelial cell necroptosis via death receptor 6 promotes metastasis
Strilić, B., Yang, L., Albarrán-Juárez, J., Wachsmuth, L., Han, K., Müller, U., Pasparakis, M., & Offermanns, S. (2016) · Nature · doi:10.1038/nature19076 · Cited by 523 · see citing works
Caspase-6 Is a Key Regulator of Innate Immunity, Inflammasome Activation, and Host Defense
Zheng, M., Karki, R., Vogel, P., & Kanneganti, T. (2020) · Cell · doi:10.1016/j.cell.2020.03.040 · Cited by 534 · see citing works
“EXPERIMENTAL MODEL AND SUBJECT DETAILS Mice—Casp6—/— (Jackson Laboratory, 006236), Nlrp3—/— (Kanneganti et al., 2006a), Casp11—/— (Kayagaki et al., 2011), Gsdmd−/− (Karki et al., 2018), Nlrc4—/— (Mariathasan et al., 2004), Aim2—/— (Jones et al., 2010), Rip3−/− (Newton et al., 2004), Rip3−/−Casp-8−/− (Oberst et al., 20…”
The diverse role of RIP kinases in necroptosis and inflammation
Silke, J., Rickard, J. A., & Gerlic, M. (2015) · Nature Immunology · doi:10.1038/ni.3206 · Cited by 522 · see citing works
Regulated cell death and inflammation: an auto-amplification loop causes organ failure
Linkermann, A., Stockwell, B. R., Krautwald, S., & Anders, H.-J. (2014) · Nature Reviews Immunology · doi:10.1038/nri3743 · Cited by 522 · see citing works
Activation of Necroptosis in Multiple Sclerosis
Ofengeim, D., Ito, Y., Najafov, A., Zhang, Y., Shan, B., DeWitt, J. P., Ye, J., Zhang, X., Chang, A., Vakifahmetoglu-Norberg, H., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.02.051 · Cited by 526 · see citing works
“Thus, similar to the requirement of caspase-8 for supporting normal embryonic development (Kaiser et al., 2011; Oberst et al., 2011; Zhang et al., 2011b), caspase-8 activity may be required to maintain normal CNS function in adult life by suppressing the activation of RIPK1 and RIPK3.”
BackgroundThe TNF Family of Ligands and Receptors: Communication Modules in the Immune System and Beyond
Dostert, C., Grusdat, M., Letellier, E., & Brenner, D. (2018) · Physiological Reviews · doi:10.1152/physrev.00045.2017 · Cited by 502 · see citing works
Caspase 8 inhibits programmed necrosis by processing CYLD
O’Donnell, M. A., Perez-Jimenez, E., Oberst, A., Ng, A., Massoumi, R., Xavier, R., Green, D. R., & Ting, A. T. (2011) · Nature Cell Biology · doi:10.1038/ncb2362 · Cited by 494 · see citing works
“Stable knockdown: L929 cells were transduced with pSUPERretro-puromycin encoding scrambled or RIPK3 targeting short hairpins as described previously 7 .”
Self-citationReceptor-interacting protein kinase 1 (RIPK1) as a therapeutic target
Mifflin, L., Ofengeim, D., & Yuan, J. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0071-y · Cited by 493 · see citing works
Koo, G.-B., Morgan, M. J., Lee, D., Kim, W.-J., Yoon, J.-H., Koo, J. S., Kim, S. H., Kim, S., Son, M. K., Hong, S. S., et al. (2015) · Cell Research · doi:10.1038/cr.2015.56 · Cited by 489 · see citing works
Inhibitor of Apoptosis Proteins Limit RIP3 Kinase-Dependent Interleukin-1 Activation
Vince, J. E., Wong, W. W.-L., Gentle, I., Lawlor, K. E., Allam, R., O'Reilly, L., Mason, K., Gross, O., Ma, S., Guarda, G., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.01.012 · Cited by 491 · see citing works
“Caspase-8 inhibits RIP3 signaling, that if left unchecked causes embryonic lethality (Kaiser et al., 2011; Oberst et al., 2011).”
BackgroundMitochondria and cell signalling
Tait, S. W. G., & Green, D. R. (2012) · Journal of Cell Science · doi:10.1242/jcs.099234 · Cited by 453 · see citing works
“This RIPK3dependent necrosis has numerous important roles in vivo during embryonic development and in host antiviral immunity (Kaiser et al., 2011; Oberst et al., 2011; Upton et al., 2010; Zhang et al., 2011).”
BackgroundSelf-citationGlover, H. L., Schreiner, A., Dewson, G., & Tait, S. W. G. (2024) · Nature Cell Biology · doi:10.1038/s41556-024-01429-4 · Cited by 489 · see citing works
Linkermann, A., Bräsen, J. H., Himmerkus, N., Liu, S., Huber, T. B., Kunzendorf, U., & Krautwald, S. (2012) · Kidney International · doi:10.1038/ki.2011.450 · Cited by 462 · see citing works
Apoptosis, necrosis and necroptosis: cell death regulation in the intestinal epithelium
Günther, C., Neumann, H., Neurath, M. F., & Becker, C. (2013) · Gut · doi:10.1136/gutjnl-2011-301364 · Cited by 462 · see citing works
“Interestingly, it turns out that there is a high degree of overlap in the molecules that regulate apoptosis and necroptosis.59 65 91e95 Under physiological conditions, TNFR ligation results in the assembly of one of the following complexes: the TNFR complex I which mediates survival functions and involves the molecule…”
BackgroundInfluentialGetting TRAIL back on track for cancer therapy
Lemke, J., von Karstedt, S., Zinngrebe, J., & Walczak, H. (2014) · Cell Death and Differentiation · doi:10.1038/cdd.2014.81 · Cited by 455 · see citing works
“Recently, it was demonstrated that DR triggering may also program cells to die in a caspase-independent, necrotic way (known as programmed necrosis or necroptosis).63 Necroptosis depends on the formation of a complex containing the kinases RIP1 and RIP3.”
BackgroundRobinson, N., McComb, S., Mulligan, R., Dudani, R., Krishnan, L., & Sad, S. (2012) · Nature Immunology · doi:10.1038/ni.2397 · Cited by 438 · see citing works
ADAR1 restricts ZBP1-mediated immune response and PANoptosis to promote tumorigenesis
Karki, R., Sundaram, B., Sharma, B. R., Lee, S., Malireddi, R. K. S., Nguyen, L. N., Christgen, S. L., Zheng, M., Wang, Y., Samir, P., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109858 · Cited by 441 · see citing works
“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript REAGENT or RESOURCE SOURCE IDENTIFIER BMDM microarray data This paper GEO: GSE184323 Expression in NCI-60 cancer cells NCI-60 database https://dtp.cancer.gov/discovery_development/ nci-60/ Experimental models: Cell lines B16-F10 ATCC Cat#…”
InfluentialNLRP12-PANoptosome activates PANoptosis and pathology in response to heme and PAMPs
Sundaram, B., Nagakannan, P., Mall, R., Wang, Y., Sarkar, R., Kim, H. J., Malireddi, R. K. S., Karki, R., Janke, L. J., Vogel, P., et al. (2023) · Cell · doi:10.1016/j.cell.2023.05.005 · Cited by 435 · see citing works
“N/A Ripk3Casp8 mice Oberst et al.(87) N/A Ripk3Casp8Casp1 mice This paper N/A Casp7 mice Lakhani et al.”
BackgroundInfluentialCaspase-8 Blocks Kinase RIPK3-Mediated Activation of the NLRP3 Inflammasome
Kang, T.-B., Yang, S.-H., Toth, B., Kovalenko, A., & Wallach, D. (2013) · Immunity · doi:10.1016/j.immuni.2012.09.015 · Cited by 419 · see citing works
Oxidative stress and regulated cell death in Parkinson’s disease
Dionísio, P. A., Amaral, J. D., & Rodrigues, C. M. P. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101263 · Cited by 436 · see citing works
Necroptosis: a crucial pathogenic mediator of human disease
Choi, M. E., Price, D. R., Ryter, S. W., & Choi, A. M. K. (2019) · JCI Insight · doi:10.1172/jci.insight.128834 · Cited by 416 · see citing works
Necroptosis in health and diseases
Zhou, W., & Yuan, J. (2014) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2014.07.013 · Cited by 414 · see citing works
“The protease activity of caspase-8 is required for suppressing necroptosis [66].”
BackgroundMechanisms of NOD-like Receptor-Associated Inflammasome Activation
Wen, H., Miao, E. A., & Ting, J. P. ‐. (2013) · Immunity · doi:10.1016/j.immuni.2013.08.037 · Cited by 415 · see citing works
Targeting RIPK1 for the treatment of human diseases
Degterev, A., Ofengeim, D., & Yuan, J. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1901179116 · Cited by 411 · see citing works
“While caspase-8 in complex with the FLIPL isoform is partially active and this heterodimer can inhibit necroptosis (42), elevated levels of FLIPS may suppress the activation of caspase-8 to promote necroptosis (22).”
BackgroundMany stimuli pull the necrotic trigger, an overview
Vanlangenakker, N., Berghe, T. V., & Vandenabeele, P. (2011) · Cell Death and Differentiation · doi:10.1038/cdd.2011.164 · Cited by 407 · see citing works
“zymatically inert homolog cellular FLICE-like inhibitory protein long (cFLIPL) an active complex that prevents RIPK3dependent necroptosis.(36) These data demonstrate that FADD and caspase-8, but also cFLIPL, counteract RIPK1- and RIPK3-dependent necroptosis during development.”
BackgroundNewton, K., & Manning, G. (2016) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014830 · Cited by 401 · see citing works
Mitochondria-mediated apoptosis in mammals
Xiong, S., Mu, T., Wang, G., & Jiang, X. (2014) · Protein & Cell · doi:10.1007/s13238-014-0089-1 · Cited by 400 · see citing works
“For example, caspase-8 activity inhibits RIP3-dependent necrosis (Oberst et al., 2011) and RIP3 in turn suppresses death receptor-mediated apoptosis (Newton et al.”
Targeting apoptotic caspases in cancer
Boice, A., & Bouchier‐Hayes, L. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2020.118688 · Cited by 402 · see citing works
A Review on Caspases: Key Regulators of Biological Activities and Apoptosis
Sahoo, G., Samal, D., Khandayataray, P., & Murthy, M. K. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03433-5 · Cited by 406 · see citing works
- Authors
- Oberst, A., Dillon, C. P., Weinlich, R., McCormick, L. L., Fitzgerald, P., Pop, C., Hakem, R., Salvesen, G. S., & Green, D. R.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Corresponding author
- Green, Douglas R.
- ORCID
- Venue
- Nature
- Published
- 2011-03-02
- Volume
- 471
- Issue
- 7338
- Pages
- 363-367
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3077893
- OpenAlex
- W1975593978
- Cited by
- 1,278
- References
- 32
- Citations by year
- 2026: 49 · 2025: 68 · 2024: 84 · 2023: 69 · 2022: 88 · 2021: 81 · 2020: 88 · 2019: 71 · 2018: 87 · 2017: 80 · 2016: 102 · 2015: 83 · 2014: 116 · 2013: 81 · 2012: 81
- FWCI
- 42.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Ariad Pharmaceuticals
- National Institutes of Health
- Canadian Institutes of Health Research
- National Cancer Institute (P01CA069381)
- National Institute of Allergy and Infectious Diseases (R01AI044828, R37AI044828)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- caspase-8, RIPK3, necroptosis, apoptosis, death receptors, Fas, embryonic lethality, Fas ligand, TNF-alpha resistance, cell death regulation, proteolytic complex, lymphocyte activation
- MeSH terms
- Animals, Cell Line, Female, Male, Necrosis, Phenotype, Tumor Necrosis Factor-alpha, Viral Proteins, Serpins, Apoptosis, fas Receptor, Multiprotein Complexes, Mice, Caspase 8, Receptor-Interacting Protein Serine-Threonine Kinases, CASP8 and FADD-Like Apoptosis Regulating Protein, Biocatalysis, Caspase Inhibitors
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